VICS June 2013 Newsletter

VICS Newsletter

The Victorian Infant Collaborative Study (VICS)

The Victorian Infant Collaborative Study (VICS) is a long term study of prematurely born infants throughout their childhood and into adulthood. VICS is a collaboration between the Royal Women’s Hospital, Mercy Hospital for Women, Monash Medical Centre and the Royal Children’s Hospital. The paediatricians, psychologists, nurses and research staff are all dedicated to improving the lives of extremely premature babies.

For over three decades VICS has been working towards better understanding the extent of long-term health problems that occur in the tiniest babies (those of birth weight <1000 g) and most premature (those of <28 weeks of gestation) born in Victoria. We are very grateful for the participation of children and families in these important clinical research studies.

VICS siblings Andrew and Cleo

Andrew born in 1991 at 27 weeks, birth weight 966g.Cleo born in 2005 at 25 weeks, birth weight 725g.
“Technology has come a long way to help little babies like Cleo and me to survive to enjoy life”

News from individual cohorts (groups)

1.Self-assessment of quality of life, health and self-esteem
The preterm adolescents reported their overall quality of life, health status and self-esteem to be similar to that reported by the controls. Within the preterm group, those who were the tiniest or most immature at birth were no different from those who were born a little bigger or more mature. A manuscript reporting these results will be published soon in a major international journal.

2.Growth
The preterm adolescents as a group start off at birth with a weight that is average if they were only born very early (before 28 weeks), below average if they were more mature (after 28 weeks) but had not grown so well before birth (with birth weights <1000 g). Either way the weight relative to babies still growing in the uterus drops quickly after birth and during the stay in the nursery. They remain lighter than expected compared with the control group for the first few years, and then gradually catch up through childhood. By 18 years of age, their weight is back to average. By 18 years the preterm adolescents’ height is about 1-2 cm shorter than would be expected from knowing their parents’ height. The parents of the preterm adolescents are a little shorter than the parents of the controls. The control adolescents are about 2-3 cm taller on average than their parents, which is consistent with the trend for each generation to be slightly taller than their parents. The weight of the control group starts off as expected, then gradually drifts upwards and by 18 years is 3-4 kilograms above the expected weight for their age and sex.

1991-92 Cohort

The 1991-92 cohort has been seen most recently at ages ranging from 14 – 20 years. As those who participated will know the evaluations and testing were very extensive and quite demanding, taking two or even three days to complete in some cases. Not everyone was able to attend, and of those who did attend, not everyone did every assessment, for various reasons, mostly related to unavailability of equipment or staff at the time of the appointments.
Of the 298 adolescents who were born either
<28 weeks or <1000 g in Victoria in 1991 or 1992, we obtained some information from 74% (220 in total).
Of the 262 adolescent born of normal birth weight
(>2499 g), who formed the control group, we obtained some information from 63% (166 in total).
In general, most adolescents who had been born very tiny or immature were doing very well, although as a group there were more health issues for them when they are compared with the controls. Results from some of the areas assessed are summarised as follows:

This growth pattern is consistent with the so-called “obesity epidemic” that has been observed in children around the world in western countries over the past few decades. A manuscript reporting these results has been published (Roberts G, et al. Growth of extremely preterm survivors from birth to 18 years of age compared with term controls. Pediatrics 2013; 131:e439-45).

3.The Lungs
Most adolescents in both groups had breathing and exercise tests that were normal for their size, age and sex. The preterm group have more trouble getting air in and out of their lungs than the control group. Those in the preterm group who had more lung problems as babies had even more trouble getting air in and out of their lungs than the preterm group who did not have as many lung problems when newborns. The results from the breathing tests at 18 were similar to what we found when the children were eight years of age. At 18 years of age, those who were smoking had breathing tests that were worse than those who were not smoking. Manuscripts reporting these results are in preparation.

4.Blood Pressure, the Heart and Blood Vessels
Blood pressure was measured over a 24-hour period by wearing a cuff on the arm attached to a blood pressure machine. Blood pressure was measured every half an hour when awake, then every hour overnight when asleep. Some also had an ultrasound of the heart, as well as tests of how blood vessels react and how stiff they are. Most adolescents in both groups had blood pressure, heart and blood vessel tests that were normal for their age.

The preterm adolescents as a group have blood pressure that is slightly higher than the control adolescents. Blood pressure measured earlier in childhood, at eight years of age was strongly related to blood pressure at 18 years. Some measurements of the heart were smaller in the preterm group than the controls, and some of the blood vessel tests suggest that the arteries of the preterm group might be stiffer than in the control group. The importance of these findings is unclear and blood pressure and blood vessel tests should be reassessed when the groups are adults. A manuscript reporting these results is in preparation.

Meg born at 26 weeks, weighing 935 g.

From Meg’s mother“Meg completed year 12 in 2010 and was dux of her school with an ATAR score of 98. She did 4 subjects……History Revolutions, Literature, Psychology and Politics. She also completed a university enhancement subject of Criminal Justice and was also dux of this class. In year 11 she completed 2 year 12 subjects of Religion and Legal Studies. Meg has taken up a double degree of Law/Psychology and is now in her third year. We are extremely proud of her determination, perseverance and achievements, but also of the way she conducts herself. Meg is a very giving and caring person with a great outlook on life and a wonderful personality. She is an absolute delight. Meg has never ceased to amaze me from the day she was born as a very tiny prem baby to the beautiful young woman she has turned into. Her determination to survive in those very early days and months has put her in good stead to achieve and become anything she wants.”

5.The Brain
Many adolescents in both groups had brain magnetic resonance imaging (MRI) scans. An understanding of changes in brain size related to preterm birth is important to help us to understand how very preterm birth affects brain growth and development. Most adolescents have brains that are normal, although a few in the preterm group have some changes related to bleeding into their brain when they were babies. As a group the brains of the preterm adolescents were smaller than the brains of the control group. Brain size is partly related to intelligence – IQ is higher in those with larger brains, to a small degree. A manuscript reporting these results is in preparation.
The parts of the brain involved in movement of the body were smaller and less well developed in the preterm group compared with controls. Those adolescents who had problems with movement had even smaller and less well-developed parts of the brain involved in movement compared with those who did not have movement problems. A manuscript reporting these results is in preparation. There are many other aspects of the brain scans that are being analysed, but the techniques are highly specialised and take a long time to complete, and hence there is much more work to do in this area over the next year or so.

6.Attention, Mood, Anxiety and other Psychiatric disorders
The preterm adolescents have more symptoms of Attention Deficit Hyperactivity Disorder (ADHD), but this is mostly due to problems with attention, rather than with hyperactivity. About one in five adolescents in both the preterm and control groups had symptoms of depression or anxiety. Very few adolescents in either group had symptoms of more severe psychiatric disturbances. Manuscripts reporting these results are in preparation

7.Vision and Visual Functioning
Most adolescents in both groups had normal vision and visual function. However more preterm adolescents had slightly more minor problems in both areas compared with controls. A manuscript reporting these results is under consideration at a journal.

8.Genetic tests
We were able to collect blood or saliva samples for genetic testing on many adolescents in both groups. At this stage we have not been able to test most of these samples as the tests are very expensive. However, on a small number of samples we have been able to find some differences between preterm and control adolescents that are related to be being born too early. This area needs more research to discover if the preliminary findings are confirmed, and to determine if they have any implications for long-term health. A manuscript reporting these results is under consideration at a journal.

1.Brain function
The rates of disabilities at age eight years in children who weighed less than 1000 g at birth were contrasted over four different eras; 1979-1980, 1985-1987, 1991-1992, and 1997. The survival rate for these children had risen from 25% for those born in 1979-1980, to 38% for those born in 1985-87, 56% for those born in 1991-92, to 73% for those born in 1997. The disability rates were consistent across each of these four eras, and higher than in controls, with approximately one in five children born under 1000g having substantial problems with thinking, hearing, walking, talking or seeing, compared with approximately one in twenty-five of children in the normal birth weight control children.

1997 Cohort

The 1997 cohort was last assessed in 2005 and 2006, when they were around eight years of age. The major areas we assessed were to do with how the brain was functioning, overall health, movement skills, and breathing tests. Of the 201 children who were born either <28 weeks or <1000 g in Victoria in 1997, we obtained some information from 94% at 8 years. Of the 199 children who were controls, who weighed more than 2499 g at birth and were born at term, we obtained some information from 87%.
Several publications have arisen from the assessments at 8 years of age, as follows:

These results are published: Roberts G, et al. Neurosensory disabilities at school age in geographic cohorts of extremely low birth weight children born between the 1970s and the 1990s. Journal of Pediatrics 2009; 154:829-34.
We know that the rate of long-term problems with brain function is more common in very preterm children the earlier they are born before birth. In the next study we compared outcome at eight years of age between those born in 1997 with those born in 1991-92, knowing that there were more high-risk survivors in 1997 born at 22-25 weeks than in 1991-92. Outcomes included blindness, deafness, cerebral palsy and intellectual impairment. Rates of disability were substantially higher in the preterm cohorts than the controls, consistent with what we have always found. The rates of major problems with thinking, hearing, walking, talking or seeing were the same for the 1997 and 1991-1992 preterm cohorts, at 19%, compared with 4% for the control children. Rates of minor problems with thinking and walking were higher in the 1997 preterm group compared with the 1991-92 preterm group. The major reason for the higher rates of disability between preterm children and control children relates to much higher rates of intellectual impairment and cerebral palsy, rather than major problems with vision or hearing.
These results are published: Roberts G, et al. Changes in neurodevelopmental outcome at age eight in geographic cohorts of children born at 22-27 weeks’ gestational age during the 1990s. Archives of Disease in Childhood Fetal and Neonatal Edition 20102; 95):F90-4

The aim of the next study was to see if diagnosis of disability at two years of age was the same as disability at eight years of age in the 1997 cohort. Those with problems at two were not necessarily those with problems at eight, and vice versa. The primary reason for the change between two and eight was because of a change in cognitive scores. This study suggests that outcomes at
2 years are not a reliable end point for follow-up studies of preterm children, and that outcomes must be determined later in childhood.
These results are published: Roberts G, et al. The stability of the diagnosis of developmental disability between ages 2 and 8 in a geographic cohort of very preterm children born in 1997. Archives of Disease in Childhood 2010; 95:786-90.

In the next study the children born in 1997 were assessed on their intellectual ability, spelling, reading, and mathematics, and on a range of behavioural outcomes including emotional symptoms, hyperactivity and peer relationships at eight years of age. Most children in both groups had normal IQs, and their tests of school performance were normal. However, the children in the preterm group were lagging behind their term born counterparts; 71% of the preterm children had a cognitive, educational or behavioural problem compared with 43% of controls, and 47% of preterm children had multiple areas of concern compared with 16% of controls.
These results are published: Hutchinson E, et al. School-age outcomes of extremely preterm or extremely low birth weight children. Pediatrics 2013; 131:e1053-1061.

2.The Lungs
Most children in both groups had breathing tests that were normal, but the preterm group had more trouble getting air in and out of their lungs than the control group. These results are similar to what we have found in preterm children born in earlier eras, when survival rates for the most extremely preterm children were very much lower. We clearly need better strategies to avoid injuring the lungs of very tiny and immature babies at birth and afterwards in the nursery.
These results are published: Hacking D, et al. Respiratory function at age 8-9 after extremely low birthweight or preterm birth in Victoria in 1997. Pediatric Pulmonology 2013, 48:449-455.

3.Overall health
Parents mostly reported that the health of their children was satisfactory, but overall the preterm group had more problems than the control group. Parents’ ratings correlated well with the clinical assessments by the paediatricians and psychologists who had evaluated the children independently of the parents’ reports. Parent reports might be useful in future to identify the children for whom a full assessment by the clinical teams would be worthwhile, rather than assessing all very preterm children, most of whom are doing well.
These results are published: Roberts G., et al. Parent-reported health in extremely preterm and extremely low-birthweight children at age 8 years compared with comparison children born at term. Developmental Medicine and Child Neurology 2011; 53:927-32.

James born in 2005 at 25 weeks, birth weight 795g

From James’s mother“We really appreciate being part of the Prem Follow Up programme. James really enjoyed doing all of the assessments. He said it should have been harder! I think he was hoping to do lots of push-ups etc.!”

4.Movement skills
In the next study, most children had normal movement skills, but three times as many preterm children (16%) were found to be clumsy on a standard test of movement ability than were observed in the control group (5%). The clumsy children also had more problems on tests of reading, spelling and arithmetic than those who were not clumsy. In this study parents’ ratings of their children’s movement skills did not correlate well with what was found on the standard movement test. Identifying clumsy children earlier and helping them with their hand and balance skills may be able to improve their school performance.
These results are published: Roberts, G., et al. Developmental coordination disorder in geographic cohorts of 8-year-old children born extremely preterm or extremely low birthweight in the 1990s. Developmental Medicine and Child Neurology 2011; 53:55-60.

What do these results mean for care of mothers and babies in the nursery?

Results from this study and others make it clear that we need to prevent the problems from developing in the preterm children, rather than treating them after they become apparent. Consequently we are currently evaluating new treatments for mothers before birth, and babies and their families after birth, which are designed to improve outcomes for preterm children and their families.

Future Studies
We anticipate assessing the children in the 1997 cohorts again later in 2013, or early in 2014; details are not yet certain, but will be finalised after we have finished assessing the children in the 2005 cohort.

As some families will be aware, a group of preterm children in this cohort is also participating in a trial, called IMPRINT, where the aim is to see if intensive memory training at home can improve school performance. This trial will take several years to complete but is important as it is one way that might help preterm children to catch up with their peers who were not born preterm.

2005 Cohort

The 2005 cohorts are currently being assessed when the children are seven to eight years of age. There are 221 preterm children and 221 controls. We are concentrating on assessing thinking ability, school progress, behaviour and breathing capacity, as we have done with earlier cohorts at the same age. We should be finished with these assessments towards the end of 2013.

A.J. born in 2005 at 26 weeks, weighing 930g.

After a long very stormy time in the nursery, now doing very well. Came all the way from Queensland for his 7-year-old assessment!

Team members from the long term follow up studies

Visit our website http://www.vics-infantstudy.org.au/
to find out more about the Victorian Infant Collaborative Study group or to update your contact details Or you can update your details by posting the form on the last page.